«Εκτίμηση κινδφνου ανάπτυξης ΗΚΚ σε ασθενείς με HCV λοίμωξη» Evaluation of HCC risk in HCV patients

Transcription

1 «Εκτίμηση κινδφνου ανάπτυξης ΗΚΚ σε ασθενείς με HCV λοίμωξη» Evaluation of HCC risk in HCV patients Δημήτρησ Ν. αμωνάκησ Γαςτρεντερολογική κλινική Πανεπιςτημίου Κρήτησ

2 Outline Epidemiology Risk factors Genetic & Viral factors Prognosis The value of SVR HCC post treatment Medications beyond antivirals

3 Epidemiology HCC incidence in HCV patients 1-3% at 30yrs With cirrhosis, de novo HCC 1-4% per year Significant role for HIV or HBV co-infection, EtOH, DM Westbrook & Dusheiko, J Hepatol 2014

4 35 centres study of complications of compensated viral cirrhosis 1308 HCV, HBV 315, 31 HCV/HBV, CPT- A HCC & decompensation more frequent with HCV Greater reduction of complications with viral suppression/ eradication Trinchet, Hepatology 2015

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8 Rise and fall of HCV related HCC ITA.LI.CA centres pts Group A: HCV (longer survival) Group B: HCV + co factors Group C: non HCV HCV-HCC patients are older, more frequently Dx under survellance and at an earlier stage HCV HCC survival is improved the recent years Cazzaqon, Liver Int 2013

9 With cirrhosis Male sex Age Severity of cirrhosis & PHT All increase risk for HCC

10 HCC in HCV-HBV co-infection Is related to: -fibrosis -duration of the disease Zampino, Ann Hepatol 2015

11 HCC in transfusion-acquired HCV Age at transfusion Male sex Zavaglia, Liver Intern 2014

12 Genetics & Virology

13 Semin Cancer Biol 2014

14 Genetic Polymorphisms and HCC in HCV IL-23R GG risk factor for HCC in 192 HCV pts Labib, Cell Immunol 2015 PNPLA3 CG/GG SNP (HALT-C trial): related with fibrosis progression, not HCC Ali, CGH 2016 Genetic heterogeneity in TNFα & IL1β gene promoters affects the risk for HCC in HCV pts Tarhuni, J Hepatol 2014 Radwan, Cytokine 2012 Functional SNP associated with expression of MHC class I polypeptiderelated sequence A (MICA) and HCC risk in HCV Lo, PLoS One 2013

15 Polymorphisms and HCC risk in HCV Polymorphisms in the TLR4 gene reduce HCC risk Agundez, Oncology 2012 Polymorphisms in TLR2 increases the risk Nischalke, Int J Cancer 2012 Polymorphisms in IFNL3 (codes IFNλ3 or IL28B) were related with HCC development (retrospective pts after Peg/Riba Rx) Chang, CGH 2015

16 Risk according to genotype Genotype 1 (the bad) Gt1a core gene nucleotide patterns associated w. HCC Korba, J Gen Virol 2015 Gt1b increases cumulative lifetime risk of HCC Lee, Int J Cancer 2015 Genotype 3 (the ugly) US Veterans 110,484 HCV+ve Gt3 significant risk for cirrhosis and HCC vs. Gt1 Association independent of Age, BMI, Antiviral Rx Kanwal, Hepatology 2014

17 Masuzaki, Hepatology 2009

18 Singh, CGH 2013

19 213 pts compensated cirrhosis + ΡΗΣ (- Vx) Median FUP 58mo: 12% diagnosed HCC 84% of ΗΚΚ in HCV HVPG>10mmHg ~ 6x HCC risk Ripoll, J Hepatol 2009

20 N=216, median FUP 10yr Prognostic index: 186 gene signature, Bil>1mg, PLT<100 K HR for HCC 3.31

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22 The treatment and the reward Treating patients before reaching severe fibrosis Treating patients with compensated cirrhosis Treating decompensated cirrhosis

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24 SVR: is it enough for HCC prevention? In studies that explored long-term end points (every fibrosis stage) SVR is related with reduction in: -all cause mortality -fibrosis -need for LTx -extrahepatic complications -hepatocarcinogenesis McCombs, JAMA Int Med 2014 Maylin, Gastroenterology Hsu, Gut 2015

25 SVR

26 30 studies, 31,528 pts, 17 countries 4.6% absolute reduction in developing HCC following SVR Pts w advanced liver disease w SVR, reduced HCC risk from 17.8% > 4.2% Morgan, Ann Intern Med 2013 Data from HALT-C trial corroborated same findings (from 8.8% > 1.1%) Lok, Gastroenterology 2011

27 Meta analysis 14 studies, encompassing 1385 pts Examined the utility of IFN based adjuvant Rx after curative resection/ ablation of HCV-associated HCC IFN treatment reduced mortality (RR 0.44, p< ) & decreased recurrence by ~30%

28 Getting into doubts

29 Aleman, CID 2013

30 Asymptomatic pts w HCV+,PCR (serum)-ve, potentially small quantities from HCV-RNA persist (though defective genomes) low grade hepatitis, low grade fibrosis (Zeuzem, Ann Intern Med 2004)

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32 Nagaoki, JGH in press

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34 Risk factors for HCC after SVR achievement (IFN based treatments) Advancing age Male sex Advanced fibrosis afp 24wk post Rx (IFN-based) Diabetes Lipids (disorders of) Alcohol Oze, CGH 2014 Hiramatsu, Hepatol Res 2015

35 HCC post DAA treatments Newer antiviral factors can eradicate the virus in the majority of patients The impact of these treatments cannot been assessed as yet Bruix, AASLD 2015

36 Cumulative incidence of HCC in HCV cirrhotics with SVR (IFN based treatments), -5 yrs: % -10 yrs: % Hiramatsu, Hepatol Res 2015

37 HCC Screening in HCV patients Surveillance and increased survival US q 6 mo (αfp) HCV +EtOH v. HCV? Surveillance in pts who are not eligible for Rx? Forner, Lancet 2012 Trinchet, Hepatology 2011 Kansagara, Ann Intern Med 2014

38 Screening for HCC in HCV - II HALT C study: overall rates for HCC in cirrhotics 7% in 4.8 yrs A significant number of pts w Ishak 3 and 4 also developed HCC Then, what defines the need for screening in cirrhotics/non-cirrhotics? Morgan, Hepatology 2010

39 Beyond antivirals

40 Cohort study, HCV pts (Taiwan) HCC cases Statin use correlated with reduced HCC risk Dose related correlation of statins and HCC risk Tsan, JCO 2013 Greater mono-unsaturated correlated with reduced HCC risk in a large European study Duarte-Salles, Int J Cancer 2015

41 Statin use correlated with: Less fibrosis progression Reduced HCC incidence Butt, Hepatology 2015

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43 Conclusions Male sex, Age, Severity of cirrhosis & PHT are risk factors for HCC development in HCV pts Genotypes 1 & 3 as well as several polymorphisms have been related to HCC SVR is an excellent end point, but does not ameliorate HCC risk in pts with severe fibrosis/cirrhosis Screening is necessary but still have open issues Statins (and? Coffee) reduce HCC risk